Anterior uveitis Granulomatous type IOP rise Transillumination defect Viral anterior uveitis?

Anterior uveitis

Granulomatous type

IOP rise

Transillumination defect

Viral anterior uveitis?

Posterior scleritis

Good general health

No rheumatoid disease

Probably idiopathic ?

• 52 year-old white male

• VA loss RE

• fascicular VFD

• swollen disc and disc hemorrhage

• AION ?

Retinitis fociImmunocompetent mangranular aspect hazy vitreousviral retinitis ?

Nightblindness

Severe VF constriction OU

Almost flat ERG OU

Hereditary retinal dystrophy ?

100µV/div

The great imitator

Philippe Kestelyn, MD, PhD, MPH

Department of Ophthalmology

Ghent University Hospital

Belgium

Jonathan Hutchinson

’’The great imitator’’

Lecture for the British Medical Society in 1879

Pubmed search

• The great imitator strikes back

• The return of the great imitator

• The new great imitator (Lyme disease)

SyphilisEpidemiology

• 12 million new cases of syphilis worldwide each year

• uncommon in Europe

• serious problem in developing countries

• serious sequelae / risk of congenital infection

Syphilis• sexually transmitted disease caused by

Treponema pallidum• penetrates intact mucous membranes and

abraded skin• incubation from 10 to 90 days• spread through the lymphatics to the

bloodstream• hematogenous dissemination• 3 stages: primary, secondary and tertiary

syphilis• 70% of patients remain in latent stage after

secondary stage• 30% go on to develop tertiary syphilis

Congenital Syphilis

• transplacental transmission of T. pallidium first 3 months

• preventable!

• intrauterine death or serious congenital abnormalities

• generalized rash, jaundice, rhinitis

• osteochondritis and X-ray abnormalities of bones in > 90%

• chorioretinitis often present

• DD rubella, CMV, toxoplasmosis

• diagnosis: FTA-ABS (IgM)

Late congenital syphilis

silent infection at birth• after 2 years :

– interstitial keratitis in 20 %

– Hutchinson’s triad:• interstitial keratitis

• notched thin upper incisors with abnormal spacing

• deafness

Ocular involvement in the different stages of syphilis

• Primary syphilis: conjunctival chancre (rare)

• Secondary syphilis: anterior and posterior involvement with pronounced inflammation

– iritis (roseolae)

– acute syphilitic posterior placoid chrioretinitis

– inner retinal punctate lesions

– retinal necrosis

• Tertiary stage: chronic anterior and posterior uveitis (chronic and mild vitritis, vasculitis, pigment epitheliopathy)

Anterior segment involvement in syphilis

• starts as unilateral iritis• contralateral eye involved in 50% of

patients • from mild nongranulomatous to

severe granulomatous • often notion of skin rash (secondary

stage)• resistant to corticosteroid treatment

• 65-year-old male

• bilateral anterior uveitis

• resistant to topical steroid treatment

• history of “allergic” skin reaction

Luetic anterior uveitis

Luetic anterior uveitis

Posterior segment complications of syphilis

• posterior scleritis• vitritis• vasculitis• venous and arterial occlusive disease• chorioretinitis , • retinal necrosis • acute syphilitic posterior placoid chorioretinitis• punctate inner retinopathy• retinal detachment with choroidal effusion• pseudoretinitis pigmentosa• macular edema, neuroretinitis • papillitis, optic perineuritis

Posterior scleritis in a TP seropositive patient

Luetic papillitis

• 52 year-old white male

• VA loss RE

• fascicular VFD

• nocturnal sweats

• skin rash 2 months ago

• VDRL +, RPR +

• LP : protein, VDRL + pleocytosis,

Luetic retinitis (HIV-)

A 32-year- old white male patient complains of hazy vision in the left eye; no general health problems, but syphilis serology strongly positive…

Before and after treatment

Full recovery of visual acuity after penicillin G therapy

Syphilis in patients with HIV infection

• recognition of concurrent infection mandatory• accelerated course of syphilis• greater likelyhood of posterior uveitis, bilateral

disease and neurosyphilis• treatment failures more common• serologic tests less reliable• “neurosyphilis treatment” for all patients ?

HIV and ocular syphilis

• Bilateral disease

• Accelerated course and extensive tissue destruction (retinalk necrosis)

• False negative serology (indirect test)

PPRE

Bilateral Luetic Uveitis: post Rx

PPLE

PPRE Inf perif LE

Bilateral Luetic Uveitis

FFA PPRE

Bilateral Luetic Uveitis: post Rx

FFA Inf perif LE

Full-Field Flash ERG

Scotopic

RE

LE

Maximal Photopic 30Hz Flicker

20µV/div

200µV/div

RE

LE

100µV/div

50µV/div

Normal Control

100µV/div

Bilateral luetic uveitisLaboratory results

• HIV positive; 624 CD4 cells /microliter• Toxoplasmosis IgG - IgM -• Epstein-Barr IgG 260 IU/ml IgM -• CMV IgG > 2000 IgM 2.0

(PCR negative) • HSV IgG 1700 IgM -• VZV IgG 1600 IgM –

• RPR negative

“Prozone” phenomenon

= disequilibrium between antibody and antigen levels

present in less than 1% of patients with secondary syphilis

false negative test

Another presentation of syphilitic posterior uveitis…

Middle aged man with mild visual impairment and bilateral inflammation

Leopard-spot like lesions on FA in the cicatricial phase

Acute syphilitic placoid pigment epitheliopathy first described by Gass considered to be pathognomonic for syphilis “leopard spots” on FA in the cicatricial phase

A 3rd rather typical presentation of posterior syphilitic involvement...

Middle aged man with mild visual impairment and bilateral inflammation

Syphilitic punctate inner retinitis in immunocompetent gay men.

Wickremasinghe et al. Ophthalmology 116:1195-1200, 2009.

Non-specific tests for syphilis

= cardiolipin from beef heart detects anti-lipid IgG and IgM formed in patients in response to: – lipoidal material released from cells damaged by the

infection – lipids in the surface of T. pallidum

• VDRL (venereal disease research lab)• RPR (rapid plasma reagin test)• decline after effective AB therapy (indicator) • false positive results

Specific tests

• = detection of antibodies to specific treponemal antigens

• FTA-ABS (fluorescent treponemal antibody absorption)

• TPHA (T. pallidum hemagglutination assay)• become positive earlier and stay positive

throughout life• cannot be used as indicators of therapeutic

response

Treatment of ocular syphilis

• same treatment regimen as for neurosyphilis• 18 to 24 million units of penicilllin G IV/day for 2

weeks• doxycycline 100 mg orally BID for 30 days• tetracycline 500 mg QID orally for 30 days• corticosteroids may be added once effective

antibiotherapy has been started

Endemic treponematoses

• Genus treponema: 4 human pathogens– T. pallidum, subspecies pallidum = venereal

sypilis– T. pallidum, subspecies endemicum = endemic

syphilis or bejel– T. pallidum, subspecies pertenue = yaws– Treponema carateum = pinta

Endemic treponematoses Common features

• Primary and secondary lesions

• After latency some patients develop laate-stage disease

• Cutaneous manifestations prominent

• Penicillin = drug of choice

• No serologic tests at present can differentiate endemic trepanomatoses from each other or from venereal syphilis

Endemic treponematoses Important differences

• Target population– Young children versus neonates and adults

• Mode of transmission– Hand-to-hand or fomites versus sexual or

transplacental

• Tertiary and systemic involvement– Rare versus common– Optic atrophy and uveitis described in endemic

syphilis (Tabara)

Take home…

• The great imitator is still there

• Syphilis serolgy is mandatory in all patients presenting with unexplained intraocular inflammation

• It is an inexpensive and reliable tool to unmask the great imitator

• If not recognized in time, syphilitic retinitis may destroy the retina in a short time period (HIV patients)

• Excellent prognosis with early and adequate treatment

Thank you !